Mac-1, a granulocyte-monocyte specific differentiation antigen containing polypeptides of 190,000 and 105,000 molecular weight, and Mac-2 and Mac-3, monocyte specific antigens of 32,000 and 110,000 molecular weight, respectively, have been identified by using rat antimouse monoclonal antibodies. All of these macrophage differentiation antigens are expressed in much greater quantities on activated macrophages than on monocytes in bone marrow, blood or spleen. Mac-1 antigen is found on tumoricidal macrophages in mice and through cross-reaction on human monocytes and natural killer cells. In the past year, Mac-2 has been found to be an inducible macrophage surface component. Mac-3 and Mac-1 are found on all macrophages. Monoclonal antibodies to Mac-1 specifically inhibit the mouse and human receptor complement for the C3bi complement fragment, allowing the study of this physiologically important receptor. Mac-3 is a heavily glycosylated antigen, and the extent of glycosylation is dependent on the state of macrophage differentiation.